Abstract
We present a novel strategy based on data-independent acquisition coupled to targeted data extraction for the detection and identification of site-specific modifications of targeted peptides in a completely unbiased manner. This method requires prior knowledge of the site of the modification along the peptide backbone from the protein of interest, but not the mass of the modification. The procedure, named multiplex adduct peptide profiling (MAPP), consists of three steps: 1) A fragment-ion tag is extracted from the data, consisting of the b-type and y-type ion series from the N and C-terminus, respectively, up to the amino-acid position that is believed to be modified; 2) MS1 features are matched to the fragment-ion tag in retention-time space, using the isolation window as a pre-filter to enable calculation of the mass of the modification; and 3) modified fragment ions are overlaid with the unmodified fragment ions to verify the mass calculated in step 2. We discuss the development, applications, and limitations of this new method for detection of unknown peptide modifications. We present an application of the method in profiling adducted peptides derived from abundant proteins in biological fluids with the ultimate objective of detecting biomarkers of exposure to reactive species.
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References
Bereman MS, Canterbury JD, Egertson JD, Horner J, Remes PM, Schwartz J, Zabrouskov V, MacCoss MJ (2012) Evaluation of front-end higher energy collision-induced dissociation on a benchtop dual-pressure linear ion trap mass spectrometer for shotgun proteomics. Anal Chem 84(3):1533–1539
Hebert AS, Richards AL, Bailey DJ, Ulbrich A, Coughlin EE, Westphall MS, Coon JJ (2014) The one hour yeast proteome. Mol Cell Proteomics 13(1):339–347
Scheltema RA, Hauschild JP, Lange O, Hornburg D, Denisov E, Damoc E, Kuehn A, Makarov A, Mann M (2014) The Q Exactive HF, a benchtop mass spectrometer with a pre-filter, high-performance quadrupole and an ultra-high-field orbitrap analyzer. Mol Cell Proteomics 13(12):3698–3708
Bereman MS, Egertson JD, Maccoss MJ (2011) Comparison between procedures using SDS for shotgun proteomic analyses of complex samples. Proteomics 11(14):2931–2935
Erde J, Loo RR, Loo JA (2014) Enhanced FASP (eFASP) to increase proteome coverage and sample recovery for quantitative proteomic experiments. J Proteome Res 13(4):1885–1895
Wisniewski JR, Zougman A, Mann M (2009) Combination of FASP and StageTip-based fractionation allows in-depth analysis of the hippocampal membrane proteome. J Proteome Res 8(12):5674–5678
Wisniewski JR, Zougman A, Nagaraj N, Mann M (2009) Universal sample preparation method for proteome analysis. Nat Methods 6(5):U359–U360
Broudy D, Killeen T, Choi M, Shulman N, Mani DR, Abbatiello SE, Mani D, Ahmad R, Sahu AK, Schilling B, Tamura K, Boss Y, Sharma V, Gibson BW, Carr SA, Vitek O, MacCoss MJ, MacLean B (2014) A framework for installable external tools in Skyline. Bioinformatics 30(17):2521–2523
Brusniak MY, Kwok ST, Christiansen M, Campbell D, Reiter L, Picotti P, Kusebauch U, Ramos H, Deutsch EW, Chen J, Moritz RL, Aebersold R (2011) ATAQS: a computational software tool for high throughput transition optimization and validation for selected reaction monitoring mass spectrometry. BMC Bioinf 12:78
Spivak M, Weston J, Bottou L, Käll L, Noble WS (2009) Improvements to the percolator algorithm for peptide identification from shotgun proteomics data sets. J Proteome Res 8(7):3737–3745
Brosch M, Yu L, Hubbard T, Choudhary J (2009) Accurate and sensitive peptide identification with mascot percolator. J Proteome Res 8(6):3176–3181
Kall L, Canterbury JD, Weston J, Noble WS, MacCoss MJ (2007) Semi-supervised learning for peptide identification from shotgun proteomics datasets. Nat Methods 4:923–925
Spivak M, Bereman MS, MacCoss MJ, Noble WS (2012) Learning score function parameters for improved spectrum identification in tandem mass spectrometry experiments. J Proteome Res 11(9):4499–4508
Ray PD, Huang B-W, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24(5):981–990
Butterfield DA, Dalle-Donne I (2012) Redox proteomics. Antioxid Redox Signal 17(11):1487–1489
Codreanu SG, Ullery JC, Zhu J, Tallman KA, Beavers WN, Porter NA, Marnett LJ, Zhang B, Liebler DC (2014) Alkylation damage by lipid electrophiles targets functional protein systems. Mol Cell Proteomics 13:849–859
Chondrogianni N, Petropoulos I, Grimm S, Georgila K, Catalgol B, Friguet B, Grune T, Gonos ES (2014) Protein damage, repair and proteolysis. Mol Asp Med 35:1–71
Jaisson S, Gillery P (2010) Evaluation of nonenzymatic posttranslational modification-derived products as biomarkers of molecular aging of proteins. Clin Chem 56(9):1401–1412
Rubino FM, Pitton M, Di Fabio D, Colombi A (2009) Toward an “omic” physiopathology of reactive chemicals: thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds. Mass Spectrom Rev 28(5):725–784
Michalski A, Cox J, Mann M (2011) More than 100,000 detectable peptide species elute in single shotgun proteomics runs but the majority is inaccessible to data-dependent LC − MS/MS. J Proteome Res 10(4):1785–1793
Bereman MS, Maclean B, Tomazela DM, Liebler DC, Maccoss MJ (2012) The development of selected reaction monitoring methods for targeted proteomics via empirical refinement. Proteomics 12(8):1134–1141
(2012) Method of the Year. Nat Methods 10(1):1
Venable JD, Dong MQ, Wohlschlegel J, Dillin A, Yates JR (2004) Automated approach for quantitative analysis of complex peptide mixtures from tandem mass spectra. Nat Methods 1(1):39–45
Gillet LC, Navarro P, Tate S, Rost H, Selevsek N, Reiter L, Bonner R, Aebersold R (2012) Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteomics 11(6):O111.016717
Egertson JD, Kuehn A, Merrihew GE, Bateman NW, MacLean BX, Ting YS, Canterbury JD, Marsh DM, Kellmann M, Zabrouskov V, Wu CC, MacCoss MJ (2013) Multiplexed MS/MS for improved data-independent acquisition. Nat Methods 10(8):744–746
Panchaud A, Scherl A, Shaffer SA, von Haller PD, Kulasekara HD, Miller SI, Goodlett DR (2009) Precursor acquisition independent from Ion count: How to dive deeper into the proteomics ocean. Anal Chem 81(15):6481–6488
Weisbrod CR, Eng JK, Hoopmann MR, Baker T, Bruce JE (2012) Accurate peptide fragment mass analysis: multiplexed peptide identification and quantification. J Proteome Res 11(3):1621–1632
Silva JC, Denny R, Dorschel CA, Gorenstein M, Kass IJ, Li G-Z, McKenna T, Nold MJ, Richardson K, Young P, Geromanos S (2005) Quantitative proteomic analysis by accurate mass retention time pairs. Anal Chem 77(7):2187–2200
Liebler DC (2008) Protein damage by reactive electrophiles: targets and consequences. Chem Res Toxicol 21(1):117–128
Wild CP (2005) Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomark Prev 14(8):1847–1850
Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (2000) Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343(2):78–85
Funk WE, Li H, Iavarone AT, Williams ER, Riby J, Rappaport SM (2010) Enrichment of cysteinyl adducts of human serum albumin. Anal Biochem 400(1):61–68
MacLean B, Tomazela DM, Shulman N, Chambers M, Finney GL, Frewen B, Kern R, Tabb DL, Liebler DC, MacCoss MJ (2010) Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 26(7):966–968
Rost H, Malmstrom L, Aebersold R (2012) A computational tool to detect and avoid redundancy in selected reaction monitoring. Mol Cell Proteomics 11(8):540–549
Rappaport SM, Li H, Grigoryan H, Funk WE, Williams ER (2012) Adductomics: characterizing exposures to reactive electrophiles. Toxicol Lett 213(1):83–90
Li H, Grigoryan H, Funk WE, Lu SS, Rose S, Williams ER, Rappaport SM (2011) Profiling Cys34 adducts of human serum albumin by fixed-step selected reaction monitoring. Mol Cell Proteomics 10(3):M110 004606
Ghosh A, Choudhury A, Das A, Chatterjee NS, Das T, Chowdhury R, Panda K, Banerjee R, Chatterjee IB (2012) Cigarette smoke induces p-benzoquinone-albumin adduct in blood serum: implications on structure and ligand binding properties. Toxicology 292(2–3):78–89
Phillips DH, Venitt S (2012) DNA and protein adducts in human tissues resulting from exposure to tobacco smoke. Int J Cancer 131(12):2733–2753
Grewal RN, El Aribi H, Harrison AG, Siu KWM, Hopkinson AC (2004) Fragmentation of protonated tripeptides: the proline effect revisited. J Phys Chem B 108(15):4899–4908
Schwartz BL, Bursey MM (1992) Some proline substituent effects in the tandem mass spectrum of protonated pentaalanine. Biol Mass Spectrom 21(2):92–96
Nagumo K, Tanaka M, Chuang VTG, Setoyama H, Watanabe H, Yamada N, Kubota K, Tanaka M, Matsushita K, Yoshida A, Jinnouchi H, Anraku M, Kadowaki D, Ishima Y, Sasaki Y, Otagiri M, Maruyama T (2014) Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases. Plos One 9(1):e85216
Chung M-K, Grigoryan H, Iavarone AT, Rappaport SM (2013) Antibody enrichment and mass spectrometry of albumin-Cys34 adducts. Chem Res Toxicol 27(3):400–407
Kall L, Storey JD, MacCoss MJ, Noble WS (2008) Posterior error probabilities and false discovery rates: two sides of the same coin. J Proteome Res 7(1):40–44
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The authors acknowledge support from NC State University and a Pilot Project Award from the Center for Human Health and the Environment which supported this work.
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Porter, C.J., Bereman, M.S. Data-independent-acquisition mass spectrometry for identification of targeted-peptide site-specific modifications. Anal Bioanal Chem 407, 6627–6635 (2015). https://doi.org/10.1007/s00216-015-8819-7
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DOI: https://doi.org/10.1007/s00216-015-8819-7